14 research outputs found
Calcium control of triphasic hippocampal STDP
Bush D, Jin Y. Calcium control of triphasic hippocampal STDP. Journal of Computational Neuroscience. 2012;33(3):495-514.Synaptic plasticity is believed to represent the neural correlate of mammalian learning and memory function. It has been demonstrated that changes in synaptic conductance can be induced by approximately synchronous pairings of pre- and post- synaptic action potentials delivered at low frequencies. It has also been established that NMDAr-dependent calcium influx into dendritic spines represents a critical signal for plasticity induction, and can account for this spike-timing dependent plasticity (STDP) as well as experimental data obtained using other stimulation protocols. However, subsequent empirical studies have delineated a more complex relationship between spike-timing, firing rate, stimulus duration and post-synaptic bursting in dictating changes in the conductance of hippocampal excitatory synapses. Here, we present a detailed biophysical model of single dendritic spines on a CA1 pyramidal neuron, describe the NMDAr-dependent calcium influx generated by different stimulation protocols, and construct a parsimonious model of calcium driven kinase and phosphatase dynamics that dictate the probability of stochastic transitions between binary synaptic weight states in a Markov model. We subsequently demonstrate that this approach can account for a range of empirical observations regarding the dynamics of synaptic plasticity induced by different stimulation protocols, under regimes of pharmacological blockade and metaplasticity. Finally, we highlight the strengths and weaknesses of this parsimonious, unified computational synaptic plasticity model, discuss differences between the properties of cortical and hippocampal plasticity highlighted by the experimental literature, and the manner in which further empirical and theoretical research might elucidate the cellular basis of mammalian learning and memory function
Bursts shape the NMDA-R mediated spike timing dependent plasticity curve: role of burst interspike interval and GABA inhibition
Spike timing dependent plasticity (STDP) is a
synaptic learning rule where the relative timing between
the presynaptic and postsynaptic action potentials determines
the sign and strength of synaptic plasticity. In its
basic form STDP has an asymmetric form which incorporates
both persistent increases and persistent decreases in
synaptic strength. The basic form of STDP, however, is not
a fixed property and depends on the dendritic location. An
asymmetric curve is observed in the distal dendrites,
whereas a symmetrical one is observed in the proximal
ones. A recent computational study has shown that the
transition from the asymmetry to symmetry is due to
inhibition under certain conditions. Synapses have also
been observed to be unreliable at generating plasticity
when excitatory postsynaptic potentials and single spikes
are paired at low frequencies. Bursts of spikes, however,\ud
are reliably signaled because transmitter release is facilitated.
This article presents a two-compartment model of the
CA1 pyramidal cell. The model is neurophysiologically
plausible with its dynamics resulting from the interplay of
many ionic and synaptic currents. Plasticity is measured by
a deterministic Ca2? dynamics model which measures the
instantaneous calcium level and its time course in the
dendrite and change the strength of the synapse accordingly.
The model is validated to match the asymmetrical
form of STDP from the pairing of a presynaptic (dendritic)
and postsynaptic (somatic) spikes as observed experimentally.
With the parameter set unchanged the model investigates
how pairing of bursts with single spikes and bursts
in the presence or absence of inhibition shapes the STDP
curve. The model predicts that inhibition strength and
frequency are not the only factors of the asymmetryto-
symmetry switch of the STDP curve. Burst interspike
interval is another factor. This study is an important first
step towards understanding how STDP is affected under
natural firing patterns in vivo